Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

LMO2 (LIM domain only 2 (rhombotin-like 1))

Written1998-06Chrysthèle Bilhou-Nabera
Cytogénétique,Laboratoire d'Hématologie-Pr RAPHAEL, Pav BROCA - 4öme étage, 78 rue du Général Leclerc, 94275 LE KREMLIN-BICETRE, France
Updated2007-11Pieter Van Vlierberghe, Jean-Loup Huret
ErasmusMC/Sophia Children's Hospital, Pediatric Oncology/Hematology, Rotterdam, The Netherlands (PVV); Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France (JLH)

(Note : for Links provided by Atlas : click)

Identity

Alias_namesRBTNL1
rhombotin-like 1
Alias_symbol (synonym)TTG2
RHOM2
RBTN2
Other aliasRBTN2 (rhombotin-2)
RBTNL1 (rhombotin-like-1)
TTG2 (T-cell translocation gene 2)
LMO2 (LIM domain only 2)
HGNC (Hugo) LMO2
LocusID (NCBI) 4005
Atlas_Id 34
Location 11p13  [Link to chromosome band 11p13]
Location_base_pair Starts at 33880123 and ends at 33891509 bp from pter ( according to hg19-Feb_2009)  [Mapping LMO2.png]
Local_order telomere LMO1 - NUP98 (11p15) - CD59 - FSHB - LMO2 - PAX6 - PDHX (11p13) centromere.
Fusion genes
(updated 2016)
CREB3L2 (7q33) / LMO2 (11p13)LMO2 (11p13) / RNF126 (19p13.3)LMO2 (11p13) / TRD ()
MBNL1 (3q25.1) / LMO2 (11p13)TRA () / LMO2 (11p13)TRB () / LMO2 (11p13)
TRBV20OR9-2 () / LMO2 (11p13)TRD () / LMO2 (11p13)

DNA/RNA

Description LMO2 belongs to a multigene family, extremely well conserved during evolution, encoding proteins containing two cystein-rich regions referred to as LIM domains: LMO1 (11p15), LMO2 (11p13), LMO3 (12p); 6 exons.
Transcription 3 transcripts: LMO2-a and LMO2-b encode the same 158-amino-acid protein; LMO2-c encodes a 151-amino-acid protein.

Protein

Description Small cystein rich protein with two tandemly arranged Zinc binding LIM domain motifs: named Lom2; 158 amino acids; 18 kDa; 48 % amino-acid identity with LMO1 protein.
LMO2 contains two transcription activating domains (one in N-term, in a prolin-rich 19 amino acid region, one in C-term) and two LIM domains as transcription repressing domains, selectively inhibiting the N-term activation domain (no effect on the C-term domain).
Expression Early expressed during development, in all tissues (roughly consistent level in central nervous system, low level in thymus).
Strongly expressed in the precursors of mixed erythrocyte/macrophage/mast, erythrocyte, megakaryocyte, neutrophil and macrophage colonies, undetectable in the mature progeny.
Expressed in early B-cells, in leukemias of both the myeloid and lymphoid lineages.
Nuclear marker in normal germinal center B-cells. Also expressed in endothelial cells. High expression in the brain; expressed in the hippocampus during development.
Localisation Nuclear.
Function
  • Hematopoiesis: LMO2 directly interacts with the basic-loop-helix protein TAL1/SCL and the GATA DNA protein GATA1. They form a transcriptional complex: LMO2 has no direct evidence in DNA binding capacity but could act as a bridging molecule bringing together different DNA binding factors (TAL1, LDB1, E12/E47, GATA1) that are essential for hematopoiesis (e.g. in the erythroid complex). This interaction is critical for the regulation of red blood cell development in early stages of hematopoiesis. TAL1 interacts specifically with the LIM domains of LMO2, which in turn binds LDB1. Because LMO2 can also bind to GATA2, a complex LMO2-GATA2 might occur at earlier stages of hematopoiesis when Gata1 is not expressed. Lmo2 has a central role in adult hematopoietic pathway regulation, on bone marrow pluripotential precursor stem cell mainly. LMO2 and TAL1 are able to partially suppress myeloid differentiation. LMO2 also interacts with retinoblastoma-binding protein 2 and elf-2 (ets transcription factor).
  • LMO2-c expression is regulated by GATA1 and PU.1; LMO2-c acts as an antagonist of LMO2-a/b, therefore blocking the transactivation of LMO2-a/b.
  • In the brain, hBEX2, LMO2, NSCL2 and LDB1 could form a similar complex.
  • Implicated in

    Note
      
    Entity t(11;14)(p13;q11)/T-cell leukaemia --> LMO2 - TCRD-A
    Disease Childhood T-cell ALL ; found in 5-10% of T-cell ALL.
    Cytogenetics A variant translocation t(7;11)(q35;p13) has been described.
    Abnormal Protein It was previously believed that LMO2 is activated after chromosomal translocation by association either the T-cell receptor a / T-cell receptor d (14q11) or T-cell receptor b gene (7q35). Chromosome breakpoints occur 25 kb upstream LMO2 gene, in a presumed transcriptional start site, inducing truncation of the promoter/control region and leading to inappropriate Lmo2 level especially in T-cells (abnormal T-cell differentiation). However, it becomes now very likely that removal of a negative regulatory element from the LMO2 locus, rather than juxtaposition to the TCRD enhancer, is the main determinant for LMO2 activation in the majority of t(11;14)(p13;q11) translocations.
      
      
    Entity del(11)(p12p13) T-cell leukaemia
    Disease Childhood T-cell ALL; found in about 5% of T-cell ALL.
    Cytogenetics Cryptic deletion that varies in size.
    Abnormal Protein LMO2 is activated through a cryptic intrachromosomal deletion, del(11)(p12p13), in which a negative regulatory element (NRE), situated upstream of the LMO2 gene, is deleted. Removal of this NRE causes activation of the proximal promoter of the LMO2 gene leading to its ectopic expression.
      
      
    Entity Germinal center B-cell lymphomas
    Disease Diffuse large-B-cell lymphomas, follicular lymphomas, Burkitt lymphomas, less often in other haematological malignancies.
    Prognosis LMO2 expression, together with BCL6, FN1, CCND2, SCYA3, and BCL2 expressions, is a predictor of outcome in diffuse large-B-cell lymphoma.
      
      
    Entity Prostate cancer
    Note Expression of LMO2 is higher in prostate tumours samples than in the normal epithelium. Moreover, overexpression of LMO2 is significantly associated with advanced tumour stage, as well as with the development of distant metastasis.
    Oncogenesis LMO2 may play an important role in prostate cancer progression, possibly via repression of E-cadherin expression.
      

    Bibliography

    Globin gene activation during haemopoiesis is driven by protein complexes nucleated by GATA-1 and GATA-2.
    Anguita E, Hughes J, Heyworth C, Blobel GA, Wood WG, Higgs DR
    The EMBO journal. 2004 ; 23 (14) : 2841-2852.
    PMID 15215894
     
    The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13.
    Boehm T, Foroni L, Kaneko Y, Perutz MF, Rabbitts TH
    Proceedings of the National Academy of Sciences of the United States of America. 1991 ; 88 (10) : 4367-4371.
    PMID 2034676
     
    Different chromosomal breakpoints impact the level of LMO2 expression in T-ALL.
    Dik WA, Nadel B, Przybylski GK, Asnafi V, Grabarczyk P, Navarro JM, Verhaaf B, Schmidt CA, Macintyre EA, van Dongen JJ, Langerak AW
    Blood. 2007 ; 110 (1) : 388-392.
    PMID 17360939
     
    Expression of rhombotin 2 in normal and leukaemic haemopoietic cells.
    Dong WF, Billia F, Atkins HL, Iscove NN, Minden MD
    British journal of haematology. 1996 ; 93 (2) : 280-286.
    PMID 8639417
     
    Negative regulatory elements are present in the human LMO2 oncogene and may contribute to its expression in leukemia.
    Hammond SM, Crable SC, Anderson KP
    Leukemia research. 2005 ; 29 (1) : 89-97.
    PMID 15541480
     
    Human Bex2 interacts with LMO2 and regulates the transcriptional activity of a novel DNA-binding complex.
    Han C, Liu H, Liu J, Yin K, Xie Y, Shen X, Wang Y, Yuan J, Qiang B, Liu YJ, Peng X
    Nucleic acids research. 2005 ; 33 (20) : 6555-6565.
    PMID 16314316
     
    The Lim-only protein LMO2 acts as a positive regulator of erythroid differentiation.
    Hansson A, Zetterblad J, van Duren C, Axelson H, Jönsson JI
    Biochemical and biophysical research communications. 2007 ; 364 (3) : 675-681.
    PMID 17964543
     
    Protein stability and transcription factor complex assembly determined by the SCL-LMO2 interaction.
    Lécuyer E, Larivière S, Sincennes MC, Haman A, Lahlil R, Todorova M, Tremblay M, Wilkes BC, Hoang T
    The Journal of biological chemistry. 2007 ; 282 (46) : 33649-33658.
    PMID 17878155
     
    Prediction of survival in diffuse large-B-cell lymphoma based on the expression of six genes.
    Lossos IS, Czerwinski DK, Alizadeh AA, Wechser MA, Tibshirani R, Botstein D, Levy R
    The New England journal of medicine. 2004 ; 350 (18) : 1828-1837.
    PMID 15115829
     
    The significance of LMO2 expression in the progression of prostate cancer.
    Ma S, Guan XY, Beh PS, Wong KY, Chan YP, Yuen HF, Vielkind J, Chan KW
    The Journal of pathology. 2007 ; 211 (3) : 278-285.
    PMID 17167821
     
    The oncoprotein LMO2 is expressed in normal germinal-center B cells and in human B-cell lymphomas.
    Natkunam Y, Zhao S, Mason DY, Chen J, Taidi B, Jones M, Hammer AS, Hamilton Dutoit S, Lossos IS, Levy R
    Blood. 2007 ; 109 (4) : 1636-1642.
    PMID 17038524
     
    TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11).
    Royer-Pokora B, Loos U, Ludwig WD
    Oncogene. 1991 ; 6 (10) : 1887-1893.
    PMID 1923511
     
    The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T-cell acute lymphoblastic leukemia.
    Van Vlierberghe P, van Grotel M, Beverloo HB, Lee C, Helgason T, Buijs-Gladdines J, Passier M, van Wering ER, Veerman AJ, Kamps WA, Meijerink JP, Pieters R
    Blood. 2006 ; 108 (10) : 3520-3529.
    PMID 16873670
     
    The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins.
    Wadman IA, Osada H, Grütz GG, Agulnick AD, Westphal H, Forster A, Rabbitts TH
    The EMBO journal. 1997 ; 16 (11) : 3145-3157.
    PMID 9214632
     
    A novel transcript of the LMO2 gene, LMO2-c, is regulated by GATA-1 and PU.1 and encodes an antagonist of LMO2.
    Wang Q, Zhang M, Wang X, Yuan W, Chen D, Royer-Pokora B, Zhu T
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2007 ; 21 (5) : 1015-1025.
    PMID 17361224
     
    The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis.
    Yamada Y, Warren AJ, Dobson C, Forster A, Pannell R, Rabbitts TH
    Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (7) : 3890-3895.
    PMID 9520463
     
    A highly conserved regulatory element controls hematopoietic expression of GATA-2 in zebrafish.
    Yang Z, Jiang H, Zhao F, Shankar DB, Sakamoto KM, Zhang MQ, Lin S
    BMC developmental biology. 2007 ; 7 : page 97.
    PMID 17708765
     

    Citation

    This paper should be referenced as such :
    Van, Vlierberghe P ; Huret, JL
    LMO2 (LIM domain only 2 (rhombotin-like 1))
    Atlas Genet Cytogenet Oncol Haematol. 2008;12(4):286-288.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/RBTN2ID34.html
    History of this paper:
    Bilhou-Nabera, C. RBTN2 (rhombotin-2). Atlas Genet Cytogenet Oncol Haematol. 1998;2(4):117-118.
    http://documents.irevues.inist.fr/bitstream/handle/2042/37451/06-1998-RBTN2ID34.pdf


    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 7 ]
      del(11)(p12p13) LMO2
    t(1;7)(p36;p12) IKZF1/PRDM16
    t(7;9)(q34;q32) TRB/TAL2
    t(7;19)(q34;p13) TRB/LYL1
    t(11;14)(p13;q11) TRD/LMO2::t(7;11)(q35;p13) TRB/LMO2
    t(11;14)(p15;q11) TRD/LMO1
    T-lineage acute lymphoblastic leukemia (T-ALL)


    External links

    Nomenclature
    HGNC (Hugo)LMO2   6642
    Cards
    AtlasRBTN2ID34
    Entrez_Gene (NCBI)LMO2  4005  LIM domain only 2
    AliasesRBTN2; RBTNL1; RHOM2; TTG2
    GeneCards (Weizmann)LMO2
    Ensembl hg19 (Hinxton)ENSG00000135363 [Gene_View]  chr11:33880123-33891509 [Contig_View]  LMO2 [Vega]
    Ensembl hg38 (Hinxton)ENSG00000135363 [Gene_View]  chr11:33880123-33891509 [Contig_View]  LMO2 [Vega]
    ICGC DataPortalENSG00000135363
    TCGA cBioPortalLMO2
    AceView (NCBI)LMO2
    Genatlas (Paris)LMO2
    WikiGenes4005
    SOURCE (Princeton)LMO2
    Genetics Home Reference (NIH)LMO2
    Genomic and cartography
    GoldenPath hg19 (UCSC)LMO2  -     chr11:33880123-33891509 -  11p13   [Description]    (hg19-Feb_2009)
    GoldenPath hg38 (UCSC)LMO2  -     11p13   [Description]    (hg38-Dec_2013)
    EnsemblLMO2 - 11p13 [CytoView hg19]  LMO2 - 11p13 [CytoView hg38]
    Mapping of homologs : NCBILMO2 [Mapview hg19]  LMO2 [Mapview hg38]
    OMIM180385   
    Gene and transcription
    Genbank (Entrez)AF257211 AK127915 BC034041 BC035607 BC042426
    RefSeq transcript (Entrez)NM_001142315 NM_001142316 NM_005574
    RefSeq genomic (Entrez)NC_000011 NC_018922 NT_009237 NW_004929378
    Consensus coding sequences : CCDS (NCBI)LMO2
    Cluster EST : UnigeneHs.34560 [ NCBI ]
    CGAP (NCI)Hs.34560
    Alternative Splicing GalleryENSG00000135363
    Gene ExpressionLMO2 [ NCBI-GEO ]   LMO2 [ EBI - ARRAY_EXPRESS ]   LMO2 [ SEEK ]   LMO2 [ MEM ]
    Gene Expression Viewer (FireBrowse)LMO2 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)4005
    GTEX Portal (Tissue expression)LMO2
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtP25791   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtP25791  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProP25791
    Splice isoforms : SwissVarP25791
    PhosPhoSitePlusP25791
    Domaine pattern : Prosite (Expaxy)LIM_DOMAIN_1 (PS00478)    LIM_DOMAIN_2 (PS50023)   
    Domains : Interpro (EBI)Znf_LIM   
    Domain families : Pfam (Sanger)LIM (PF00412)   
    Domain families : Pfam (NCBI)pfam00412   
    Domain families : Smart (EMBL)LIM (SM00132)  
    Conserved Domain (NCBI)LMO2
    DMDM Disease mutations4005
    Blocks (Seattle)LMO2
    PDB (SRS)2XJY    2XJZ    2YPA    4KFZ   
    PDB (PDBSum)2XJY    2XJZ    2YPA    4KFZ   
    PDB (IMB)2XJY    2XJZ    2YPA    4KFZ   
    PDB (RSDB)2XJY    2XJZ    2YPA    4KFZ   
    Structural Biology KnowledgeBase2XJY    2XJZ    2YPA    4KFZ   
    SCOP (Structural Classification of Proteins)2XJY    2XJZ    2YPA    4KFZ   
    CATH (Classification of proteins structures)2XJY    2XJZ    2YPA    4KFZ   
    SuperfamilyP25791
    Human Protein AtlasENSG00000135363
    Peptide AtlasP25791
    HPRD01586
    IPIIPI00016852   IPI00915342   IPI00926017   
    Protein Interaction databases
    DIP (DOE-UCLA)P25791
    IntAct (EBI)P25791
    FunCoupENSG00000135363
    BioGRIDLMO2
    STRING (EMBL)LMO2
    ZODIACLMO2
    Ontologies - Pathways
    QuickGOP25791
    Ontology : AmiGORNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  RNA polymerase II activating transcription factor binding  transcriptional activator activity, RNA polymerase II transcription factor binding  transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding  protein binding  nucleus  transcription factor complex  multicellular organism development  zinc ion binding  mRNA transcription from RNA polymerase II promoter  bHLH transcription factor binding  positive regulation of transcription from RNA polymerase II promoter  cofactor binding  E-box binding  cellular response to thyroid hormone stimulus  
    Ontology : EGO-EBIRNA polymerase II regulatory region sequence-specific DNA binding  RNA polymerase II transcription factor activity, sequence-specific DNA binding  RNA polymerase II activating transcription factor binding  transcriptional activator activity, RNA polymerase II transcription factor binding  transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding  protein binding  nucleus  transcription factor complex  multicellular organism development  zinc ion binding  mRNA transcription from RNA polymerase II promoter  bHLH transcription factor binding  positive regulation of transcription from RNA polymerase II promoter  cofactor binding  E-box binding  cellular response to thyroid hormone stimulus  
    Pathways : KEGGTranscriptional misregulation in cancer   
    NDEx NetworkLMO2
    Atlas of Cancer Signalling NetworkLMO2
    Wikipedia pathwaysLMO2
    Orthology - Evolution
    OrthoDB4005
    GeneTree (enSembl)ENSG00000135363
    Phylogenetic Trees/Animal Genes : TreeFamLMO2
    HOVERGENP25791
    HOGENOMP25791
    Homologs : HomoloGeneLMO2
    Homology/Alignments : Family Browser (UCSC)LMO2
    Gene fusions - Rearrangements
    Fusion : MitelmanTRD/LMO2 [-/11p13]  [t(11;14)(p13;q11)]  
    Fusion : TICdbTCR [LMO2]  -  11p13 []
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerLMO2 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)LMO2
    dbVarLMO2
    ClinVarLMO2
    1000_GenomesLMO2 
    Exome Variant ServerLMO2
    ExAC (Exome Aggregation Consortium)LMO2 (select the gene name)
    Genetic variants : HAPMAP4005
    Genomic Variants (DGV)LMO2 [DGVbeta]
    DECIPHER (Syndromes)11:33880123-33891509  ENSG00000135363
    CONAN: Copy Number AnalysisLMO2 
    Mutations
    ICGC Data PortalLMO2 
    TCGA Data PortalLMO2 
    Broad Tumor PortalLMO2
    OASIS PortalLMO2 [ Somatic mutations - Copy number]
    Cancer Gene: CensusLMO2 
    Somatic Mutations in Cancer : COSMICLMO2  [overview]  [genome browser]  [tissue]  [distribution]  
    Mutations and Diseases : HGMDLMO2
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    BioMutasearch LMO2
    DgiDB (Drug Gene Interaction Database)LMO2
    DoCM (Curated mutations)LMO2 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)LMO2 (select a term)
    intoGenLMO2
    NCG5 (London)LMO2
    Cancer3DLMO2(select the gene name)
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Diseases
    OMIM180385   
    Orphanet
    MedgenLMO2
    Genetic Testing Registry LMO2
    NextProtP25791 [Medical]
    TSGene4005
    GENETestsLMO2
    Huge Navigator LMO2 [HugePedia]
    snp3D : Map Gene to Disease4005
    BioCentury BCIQLMO2
    ClinGenLMO2
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD4005
    Chemical/Pharm GKB GenePA30408
    Clinical trialLMO2
    Miscellaneous
    canSAR (ICR)LMO2 (select the gene name)
    Probes
    Litterature
    PubMed105 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineLMO2
    EVEXLMO2
    GoPubMedLMO2
    iHOPLMO2
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

    Search in all EBI   NCBI

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Wed Apr 12 11:38:37 CEST 2017

    Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.